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Am J Physiol Regul Integr Comp Physiol 285: R1473-R1480, 2003. First published August 21, 2003; doi:10.1152/ajpregu.00269.2003
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NEUROHUMORAL CONTROL OF CIRCULATION AND HYPERTENSION

Thyroxine-induced cardiac hypertrophy: influence of adrenergic nervous system versus renin-angiotensin system on myocyte remodeling

L. W. Hu,1 L. A. Benvenuti,3 E. A. Liberti,1 M. S. Carneiro-Ramos,2 and M. L. M. Barreto-Chaves1

1Department of Anatomy and 2Department of Histology and Embryology, Institute of Biomedical Sciences, Universidade de São Paulo, São Paulo 05508-900; and 3Heart Institute (InCor) University of São Paulo Medical School, São Paulo 05403-000, Brazil

Submitted 14 May 2003 ; accepted in final form 18 August 2003

The present study assessed the possible involvement of the renin-angiotensin system (RAS) and the sympathetic nervous system (SNS) in thyroxine (T4)-induced cardiac hypertrophy. Hemodynamic parameters, heart weight (HW), ratio of HW to body weight (HW/BW), and myocyte width were evaluated in absence of thyroid hormone (hypothyroidism) and after T4 administration. Male Wistar rats were used. Some were subjected to thyroidectomies, whereas hyperthyroidism was induced in others via daily intraperitoneal injection of T4 (25 or 100 µg · 100 g BW-1 · day-1) for 7 days. In some cases, T4 administration was combined with the angiotensin I-converting enzyme inhibitor enalapril (Ena), with the angiotensin type 1 (AT1) receptor blocker losartan (Los) or with the {beta}-adrenergic blocker propanolol (Prop). Hemodynamics and morphology were then evaluated. Systolic blood pressure (SBP) was not altered by administration of either T4 alone or T4 in combination with the specific inhibitors. However, SBP decreased significantly in hypothyroid rats. An increased heart rate was seen after administration of either T4 alone or T4 in combination with either Los or Ena. Although the higher dose of T4 significantly increased HW, HW/BW increased in both T4-treated groups. Ena and Prop inhibited the increase in HW or HW/BW in hyperthyroid rats. Morphologically, both T4 dose levels significantly increased myocyte width, an occurrence prevented by RAS or SNS blockers. There was a good correlation between changes in HW/BW and myocyte width. These results indicate that T4-induced cardiac hypertrophy is associated with both the SNS and the RAS.

cardiac myocytes; thyroid hormone; angiotensin-converting enzyme; angiotensin II receptors


Address for reprint requests and other correspondence: M. L. M. Barreto-Chaves, Laboratory of Cellular Biology and Functional Anatomy, Dept. of Anatomy, Biomedical Sciences Institute, Univ. of São Paulo, Av. Prof. Lineu Prestes 2415, Cidade Universitária, São Paulo, SP 05508-900, Brazil (E-mail: mchaves{at}usp.br).




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